Liu Xing, Jiang Wei-zhong, Guan Guo-xian, Chen Zhi-fen, Chi Pan, Lu Hui-shan
Department of Gastrointestinal Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2013 Mar;16(3):221-5.
To investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.
Clinical data of 48 patients with imatinib-resistant GIST received sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian Medical University were analyzed retrospectively. Eighteen patients received 50 mg/d of sunitinib in a protocol of 4/2 (4 weeks on and 2 weeks off) [50 mg/d (4/2)], and 30 patients received a protocol of 37.5 mg of sunitinib continuous daily dose (37.5 mg/d CDD).
The median duration of sunitinib administration of all the 48 patients was 56 weeks, and the short-term efficacy was evaluated at 24 weeks after the initial treatment according to the Choi criteria. The response rate was 27.1% (13/48), including 1 case with complete response (CR), 12 cases with partial response (PR), and 21 cases with stationary disease (SD). The disease control rate was 70.8% (34/48). The mean follow-up time of 48 patients was 89 weeks. The median progression-free survival (PFS) and overall survival (OS) were 48 weeks and 92 weeks respectively. Stratified analyses indicated that the median PFS of patients previously treated by imatinib 400 mg/d and >400 mg/d were 53 weeks and 35 weeks respectively (P=0.018), and the median OS of these two groups were 157 weeks and 71 weeks respectively (P=0.003). Patients with exon 11 mutations had a significantly shorter OS compared with those with exon 9 mutations (71 weeks vs 157 weeks, P=0.008). Hand-foot syndrome was the most common adverse effect (25/48, 52.1%), followed by nausea (24/48, 50.0%), fatigue (23/48, 47.9%), neutropenia(21/48, 41.7%). The sub-group analysis of two protocols of sunitinib administration showed that the incidence of diarrhea and hand-foot syndrome were higher in 50 mg/d (4/2) group than those in 37.5 mg/d CDD group (P=0.027, P=0.048).
Sunitinib is effective for the patients with imatinib-resistant GIST. After 400 mg/d imatinib treatment failure, sunitinib should be prescribed instead of increased dosage of imatinib. Patients with KIT exon 9 mutations present better prognosis than those with KIT exon 11 mutations. The protocol of sunitinib 37.5 mg/d CDD possesses better safety.
探讨舒尼替尼治疗对伊马替尼耐药的胃肠道间质瘤（GIST）患者的疗效及安全性。
回顾性分析2008年5月至2012年4月在福建医科大学附属协和医院接受舒尼替尼治疗的48例伊马替尼耐药GIST患者的临床资料。18例患者接受50mg/d舒尼替尼按4/2方案（4周用药，2周停药）[50mg/d（4/2）]治疗，30例患者接受舒尼替尼每日持续剂量37.5mg（37.5mg/d CDD）方案治疗。
48例患者舒尼替尼给药的中位持续时间为56周，根据Choi标准在初始治疗24周后评估短期疗效。有效率为27.1%（13/48），包括1例完全缓解（CR），12例部分缓解（PR），21例病情稳定（SD）。疾病控制率为70.8%（34/48）。48例患者的平均随访时间为89周。中位无进展生存期（PFS）和总生存期（OS）分别为48周和92周。分层分析表明，既往接受400mg/d和>400mg/d伊马替尼治疗的患者，中位PFS分别为53周和35周（P=0.018），两组的中位OS分别为157周和71周（P=0.003）。KIT外显子11突变的患者与KIT外显子9突变的患者相比，OS显著缩短（71周对157周，P=0.008）。手足综合征是最常见的不良反应（25/48，52.1%），其次是恶心（24/48，50.0%）、疲劳（23/48，47.9%）、中性粒细胞减少（21/48，41.7%）。舒尼替尼两种给药方案的亚组分析显示，50mg/d（4/2）组腹泻和手足综合征的发生率高于37.5mg/d CDD组（P=0.027，P=0.048）。
舒尼替尼对伊马替尼耐药的GIST患者有效。伊马替尼400mg/d治疗失败后，应改用舒尼替尼而非增加伊马替尼剂量。KIT外显子9突变的患者比KIT外显子11突变的患者预后更好。舒尼替尼37.5mg/d CDD方案安全性更好。
